Binding and uptake of the toxic lectin modeccin by baby hamster kidney (BHK) cells. Isolation of mutants defective in the internalization of modeccin.
The effects of the toxic lectins, ricin and modeccin, on baby hamster kidney (BHK) cells have been compared. Modeccin is about 20-50 times more toxic to BHK cells than ricin. Binding studies showed that there are 10(5) to 2 X 10(5) modeccin binding sites/cell compared with approximately 10(7) binding sites for ricin. Inhibition studies with galactosides indicate that both N- and O-glycans with terminal galactosyl residues are effective inhibitors of modeccin binding. Surface-bound modeccin, at 0 degrees C, was found to be very rapidly endocytosed (75-80% in 10 min) when cells were warmed to 37 degrees C. Two modeccin-resistant BHK cell lines have been isolated and characterized. These mutants bind normal levels of modeccin and retain sensitivity to the toxic action of ricin. Both cell lines were shown to be defective in their ability to internalize modeccin. Also, these mutants are morphologically different from parental cells as they align and elongate very prominently at low cell densities. These mutants will be very useful in understanding the mechanism of uptake and transport of modeccin.


Comparison of anterior and posterior iliac crest bone grafts in terms of harvest-site morbidity and functional outcomes.
Previous studies have demonstrated high complication rates after harvest of iliac crest bone grafts. This study was undertaken to compare the morbidity related to the harvest of anterior iliac crest bone graft with that related to the harvest of posterior iliac crest bone graft and to determine differences in functional outcome. The medical records of eighty-eight consecutive patients who had undergone a total of 108 iliac crest bone-grafting procedures for the treatment of chronic osteomyelitis from 1991 to 1998 were retrospectively reviewed. Demographic characteristics, the location of the harvest, the volume of bone graft that was harvested, the estimated blood loss, and postoperative complications were recorded. Fifty-eight patients completed a questionnaire pertaining to postoperative and residual pain, sensory disturbances, functional limitations, cosmetic appearance, and overall satisfaction with the bone-graft harvesting procedure. Sixty-six anterior and forty-two posterior bone-graft harvest sites were evaluated at a minimum of two years after the operation. A major complication was associated with 8% (five) of the sixty-six anterior sites and 2% (one) of the forty-two posterior sites. The rates of minor complications were 15% (ten) and 0%, respectively. In the series as a whole, there were ten minor complications (9%) and six major complications (6%). The rates of both minor complications (p = 0.006) and all complications (p = 0.004) were significantly higher after the anterior harvest procedures than they were after the posterior procedures. The postoperative pain at the donor site was significantly more severe (p = 0.0016) and of significantly greater duration (p = 0.0017) after the anterior harvests. No patient reported functional limitations at the latest follow-up evaluation. In this series, the complication rate was lower than those previously reported by other investigators. Harvest of a posterior iliac crest bone graft was associated with a significantly lower risk of postoperative complications. On the basis of the results of this study, we recommend that iliac crest bone graft be harvested posteriorly whenever possible.


mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets.
Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression.


The contributions of virtual colonoscopy to laparoscopic colorectal surgery.
Operative tumor or polypectomy site localization and synchronous colonic lesions are challenging problems especially in laparoscopic surgery. We designed this prospective study to determine the contributions of virtual colonoscopy to laparoscopic colorectal surgery. Virtual colonoscopy was performed in 40 consecutive patients who had undergone laparoscopic resection for colorectal neoplasm. Preoperative findings of optical colonoscopy and virtual colonoscopy, operative data, tumor localizations and histopathologic findings were assessed. Accuracy rates for virtual colonoscopy and optical colonoscopy were 97.5% and 55%, respectively (P<0.05). Polypectomy site was localized with virtual colonoscopy in five patients. There were nine partially obstructing tumors that did not allow optical endoscope passage. Four of six synchronous tumors (one tumor and three polyps) couldn't be shown with optical colonoscopy because of distal obstructing tumor. Histopathologic investigations revealed adenocarcinoma (n=34), adenoma demonstrating low-grade dysplasia (n=3) and high-grade dysplasia (n=2) and neuroendocrine carcinoma (n=1). Mean tumor size was 4 (1.5-10) cm. Mean proximal and distal surgical margins were 15 (5-36) cm and 7.3 (0.8-27) cm, respectively. Overall patient preference was 87.5% for virtual colonoscopy. Correct localization of colorectal neoplasm or polypectomy site is mandatory before laparoscopic colorectal surgery. Virtual colonoscopy is a safe, minimally invasive three-dimensional imaging method and may be an alternative localization technique.


Simulation-based training is associated with lower risk-adjusted mortality in ACS pediatric TQIP centers.
Although use of simulation-based team training for pediatric trauma resuscitation has increased, its impact on patient outcomes has not yet been shown. The purpose of this study was to determine the association between simulation use and patient outcomes. Trauma centers that participate in the American College of Surgeons (ACS) Pediatric Trauma Quality Improvement Program (TQIP) were surveyed to determine frequency of simulation use in 2014 and 2015. Center-specific clinical data for 2016 and 2017 were abstracted from the ACS TQIP registry (n = 57,916 patients) and linked to survey responses. Center-specific risk-adjusted mortality was estimated using multivariable hierarchical logistic regression and compared across four levels of simulation-based training use: no training, low-volume training, high-volume training, and survey nonresponders (unknown training use). Survey response rate was 75% (94/125 centers) with 78% of the responding centers (73/94) reporting simulation use. The average risk-adjusted odds of mortality was lower in centers with a high volume of training compared with centers not using simulation (odds ratio, 0.58; 95% confidence interval, 0.37-0.92). The times required for resuscitation processes, evaluations, and critical procedures (endotracheal intubation, head computed tomography, craniotomy, and surgery for hemorrhage control) were not different between centers based on levels of simulation use. Risk-adjusted mortality is lower in TQIP-Pediatric centers using simulation-based training, but this improvement in mortality may not be mediated by a reduction in time to critical procedures. Further investigation into alternative mediators of improved mortality associated with simulation use is warranted, including assessment of resuscitation quality, improved communication, enhanced teamwork skills, and decreased errors. Therapeutic/care management, Level III.


Plasma proteome response to severe burn injury revealed by 18O-labeled "universal" reference-based quantitative proteomics.
A burn injury represents one of the most severe forms of human trauma and is responsible for significant mortality worldwide. Here, we present the first quantitative proteomics investigation of the blood plasma proteome response to severe burn injury by comparing the plasma protein concentrations of 10 healthy control subjects with those of 15 severe burn patients at two time-points following the injury. The overall analytical strategy for this work integrated immunoaffinity depletion of the 12 most abundant plasma proteins with cysteinyl-peptide enrichment-based fractionation prior to LC-MS analyses of individual patient samples. Incorporation of an 18O-labeled "universal" reference among the sample sets enabled precise relative quantification across samples. In total, 313 plasma proteins confidently identified with two or more unique peptides were quantified. Following statistical analysis, 110 proteins exhibited significant abundance changes in response to the burn injury. The observed changes in protein concentrations suggest significant inflammatory and hypermetabolic response to the injury, which is supported by the fact that many of the identified proteins are associated with acute phase response signaling, the complement system, and coagulation system pathways. The regulation of approximately 35 proteins observed in this study is in agreement with previous results reported for inflammatory or burn response, but approximately 50 potentially novel proteins previously not known to be associated with burn response or inflammation are also found. Elucidating proteins involved in the response to severe burn injury may reveal novel targets for therapeutic interventions as well as potential predictive biomarkers for patient outcomes such as multiple organ failure.


Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles.
To investigate how changes in the gastrointestinal tract (GIT) microbiota profile may influence nutraceutical efficacy in osteoarthritis (OA) and allow the formulation of a hypothesis that explains in part the inconsistent and contentious findings from OA clinical studies with green-lipped mussel (GLM) and glucosamine. A non-blinded randomised clinical trial was conducted with 38 subjects diagnosed with knee OA. Each participant received either 3,000 mg/day of a whole GLM extract or 3,000 mg/day of glucosamine sulphate (GS), p.o. for 12 weeks. Faecal microbial analyses were carried out after collecting stools at T (0) and T (12) weeks. Additional pharmacometric measures were obtained from changes in arthritic scores in the Western Ontario McMaster Universities Arthritis Index (WOMAC) and the Lequesne algofunctional indices and the Gastrointestinal Symptom Rating Scale (GSRS). An intention-to-treat analysis was employed and participant data collected at T (0), T (6) and T (12) weeks. There were no statistically significant changes in bacterial growth patterns determined by the Wilcoxon test. In both groups there was a trend towards a decrease in Clostridium and Staphylococcus species and increase in Lactobacillus, Streptococcus and Eubacterium species. In the GLM group Bifidobacterium tended to increase and Enterococcus and yeast species to decrease. The GS-treated group demonstrated a trend towards a decrease in Bacteroides and an increase in yeasts and Coliforms species, most notably Escherichia coli. We further confirm significant improvement (p < 0.05) in all OA outcome measures from T (0) to T (12) weeks for both the GLM and GS groups. The GSRS scores indicated that GIT function significantly improved over the 12 weeks duration with GLM and GS supplementation. Both GLM and GS reduced OA symptoms and non-significantly altered the gut microbiota profile from baseline. Changes in the microbiota profiles occurred in both treatment groups; the most notable being a reduction in the Clostridia sp. This study suggests that nutritional supplements such as GLM and GS may regulate some of the metabolic and immunological activities of the GIT microbiota. The decrease in Clostridia, a potent modulator of colonic Th17 and CD4+ regulatory T cells, was consistent with a decrease in inflammation; improved GSRS scores and OA symptoms for these OA participants. The GIT microbiota may be important factor in the first-pass metabolism of these nutraceuticals.


Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer.
Novel strategies for the therapy of recurrent ovarian cancer are warranted. We report a study of a combinatorial approach encompassing dendritic cell (DC)-based autologous whole tumor vaccination and anti-angiogenesis therapy, followed by the adoptive transfer of autologous vaccine-primed CD3/CD28-co-stimulated lymphocytes. Recurrent ovarian cancer patients for whom tumor lysate was available from prior cytoreductive surgery underwent conditioning with intravenous bevacizumab and oral metronomic cyclophosphamide, sequentially followed by (1) bevacizumab plus vaccination with DCs pulsed with autologous tumor cell lysate supernatants, (2) lymphodepletion and (3) transfer of 5 × 109 autologous vaccine-primed T-cells in combination with the vaccine. Feasibility, safety as well as immunological and clinical efficacy were evaluated. Six subjects received this vaccination. Therapy was feasible, well tolerated, and elicited antitumor immune responses in four subjects, who also experienced clinical benefits. Of these, three patients with residual measurable disease received outpatient lymphodepletion and adoptive T-cell transfer, which was well tolerated and resulted in a durable reduction of circulating regulatory T cells and increased CD8+ lymphocyte counts. The vaccine-induced restoration of antitumor immunity was achieved in two subjects, who also demonstrated clinical benefits, including one complete response. Our findings indicate that combinatorial cellular immunotherapy for the treatment of recurrent ovarian cancer is well tolerated and warrants further investigation. Several modifications of this approach can be envisioned to optimize immunological and clinical outcomes.


Infusions of fluorouracil and leucovorin: effects of the timing and semi-intermittency of drug delivery.
Preclinical and clinical studies have demonstrated that the circadian modulation of 5-FU delivery may reduce toxicities and improve antitumor activity. However, the relative importance of the timing of 5-FU delivery has not been clinically addressed. The aims of this study were to determine the toxicities, the maximum tolerable doses and the activity of a regimen with 5-fluorouracil (5-FU) and leucovorin (LV) administered as a 14-day continuous infusion according to a flat or three different chronomodulated rhythms in patients with metastatic gastrointestinal carcinomas. A total of 113 patients entered the study and their characteristics were comparable among the four groups. Toxicities included mainly stomatitis and diarrhea, and a reduced toxicity was observed in all the three chronogroups that allowed the delivery of higher dose intensities. Response rates were not significantly different among the four groups. These results suggest that a reduction in 5-FU+LV toxicity and an increase in 5-FU dose intensity can be obtained by a nonsinusoidally circadian modulated infusion. However, the reduction in toxicity observed seems to be dependent mainly on the quasi-intermittency and not on the timing of 5-FU+LV delivery.


Cytological Study of Topical Effect of Azelastine Hydrochloride on the Nasal Mucous Membrane Cells in Various Nasal Rhinitis Types.
Previous reports on the benefits of using local therapy with azelastine in rhinitis focus on the assessment of clinical symptoms and the analysis of nasal lavage for the presence of inflammatory cells and the expression of adhesion molecules. Little attention has been paid to studies assessing the effect of azelastine on individual cytotypes of the nasal mucosa, especially epithelial cells, also in the context of inducing morphological changes. The aim of this study was the cytological analysis of swabs taken from the surface of the nasal mucosa of patients with allergic rhinitis (AR) and nonallergic/vasomotor rhinitis (NAR/VMR) who were subjected to 4 weeks of therapy with azelastine and then comparing the obtained results with the pre-treatment condition. The technique of obtaining materials for cytoanalysis included sampling, staining of smears, microscopic analysis, and preparation of cytograms. Our studies confirmed the therapeutic benefits of azelastine in both study groups. Significant changes were demonstrated, confirming the regeneration of ciliated cells and the induction of autophagy and apoptosis in epithelial cells. Such changes indicate new mechanisms of action of azelastine, which play a significant role in restoring homeostasis in the nasal mucosa. The presented research also results in a detailed description of cytological changes in both studied rhinitis types, which complements the knowledge regarding prognostic indicators.


Impact of COVID-19 on Immunization Services for Maternal and Infant Vaccines: Results of a Survey Conducted by Imprint-The Immunising Pregnant Women and Infants Network.
The COVID-19 pandemic response has caused disruption to healthcare services globally, including to routine immunizations. To understand immunization service interruptions specifically for maternal, neonatal and infant vaccines, we captured the local experiences of members of the Immunising Pregnant Women and Infants Network (IMPRINT) by conducting an online survey over 2-weeks in April 2020. IMPRINT is a global network of clinicians and scientists working in maternal and neonatal vaccinology. The survey included discrete questions to quantify the extent of disruption as well as free-text options to explore the reasons behind reported disruptions. Of the 48 responses received, the majority (75%) were from low-and-middle-income countries (LMICs). Of all respondents, 50% or more reported issues with vaccine delivery within their country. Thematic analysis identified three key themes behind immunization disruption: "access" issues, e.g., logistical barriers, "provider" issues, e.g., staff shortages and user "concern" about attending immunization appointments due to COVID-19 fear. Access and provider issues were more commonly reported by LMIC respondents. Overall, respondents reported uncertainty among parents and healthcare providers regarding routine immunization. We conclude that further quantification of routine vaccination disruption is needed, alongside health service prioritization, logistical support and targeted communication strategies to reinforce routine immunizations during the COVID-19 response.


[Diffuse interstitial pulmonary amyloidosis (author's transl)].
A 56-year-old woman developed diffuse interstitial pulmonary amyloidosis and died two years after the onset of dyspneic symptoms. Lung biopsy confirmed the amyloid nature of the reticulonodular lesions, which were at the origin of the mixed restrictive and obstructive ventilatory deficiency. Investigations showed an obvious hypogamma globulinemia but the etiology of the affection remained unknown. Pathological examination revealed massive infiltration of amyloid material in the lungs, no involvement of the heart, what was unexpected, and minimal deposits in the mediastinal lymph nodes kidneys, and spleen. An immunofluorescence study of the pulmonary amyloid deposits was performed. The authors emphasize the rarity of such diffuse interstitial pulmonary amyloid lesions which differ greatly from nodular amyloidosis and upper respiratory tract amyloid infections.


Lack of association of apolipoprotein E epsilon4 allele dose with cerebral glucose metabolism in Alzheimer disease.
Parietal cerebral glucose metabolism is reduced before substantial impairments appeared in subjects carrying the apolipoprotein E (APOE) epsilon4 allele, but the effect of the APOE epsilon4 allele on cerebral metabolism in Alzheimer disease (AD) is still undetermined. To investigate the effect of the APOE epsilon4 allele on cerebral metabolism in AD, we examined regional cerebral glucose metabolism in 83 patients with AD by using 18F-fluorodeoxyglucose and positron emission tomography. Cerebral glucose metabolism in the fronto-parieto-temporal association and limbic cortices was significantly decreased in the AD patients compared with 26 age- and sex-matched normal controls. Regional cerebral glucose metabolic rate was not correlated significantly with the number of APOE epsilon4 alleles in any region, which was consistent even after controlling the effects of age, sex, and severity of dementia, and in a subgroup analysis of those aged between 60 and 75. These results supported the view that the APOE epsilon4 allele is not associated with specific deficits in brain metabolism in AD despite evidence of preclinical alterations.


Relationship of 1-beta-D-arabinofuranosylcytosine in plasma to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in leukemic cells during treatment with high-dose 1-beta-D-arabinofuranosylcytosine.
The pharmacokinetic values of 1-beta-D-arabinofuranosylcytosine (ara-C) in plasma and its active metabolite 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) in circulating blast cells were studied in 11 patients with acute leukemia. ara-C was administered as a 2-h infusion (3 g/m2) followed in 12 to 24 h by a continuous infusion for 4 days in 10 patients and for 7 days in one. A steady-state concentration of ara-C in plasma (94 +/- 32 microM) was reached by the end of the 2-h infusion. Its elimination was biphasic with an initial and terminal t1/2 of 0.44 +/- 0.10 h and 2.8 +/- 0.9 h, respectively. The accumulation of ara-CTP in leukemic cells was linear and continued for up to 2 h after the bolus infusion. ara-CTP elimination was monophasic with a median t1/2 of 3.4 h (range, 1.25 to 18.9 h). The disposition of ara-C and 1-beta-D-arabinofuranosyluracil during continuous infusion was linear with dose rate over the dose range of 70 to 3000 mg/m2/day. The area under the concentration versus time curve for ara-CTP in leukemic cells was not related to the dose infused, but rather appeared to be intrinsic to the cells of each individual. As a general finding, the pharmacokinetic values of ara-CTP in circulating blasts were more heterogeneous than those of ara-C in plasma. There were marked differences in the absolute concentrations of ara-C in plasma and ara-CTP in leukemic cells at different times after the bolus infusion and also during continuous infusion. No correlation was evident between the determinants of ara-C pharmacokinetic values and those of ara-CTP. Thus, it is concluded that the pharmacokinetics of ara-C in plasma cannot predict for the metabolism of ara-CTP in leukemic cells.


The Turkish version of the Modified Falls Efficacy Scale: reliability and validity from the viewpoint of balance
The factors associated with fall-related self-efficacy should be addressed, especially in the elderly. The Modified Falls Efficacy Scale (MFES) is a simple instrument with good scaling properties and reliability. The aim of the present study was to determine the reliability and the validity of the Turkish version of the MFES from the viewpoint of balance. In this study, 164 participants aged >65 years were included. The use of walking aids and assistive devices, history and frequency of falls in the previous year, living environment, and exercise habits were noted. Balance and risk of falling were assessed with the Berg Balance Scale (BBS). A forward-backward translation procedure was used for the Turkish version of the MFES. None of the 14 items in the MFES were modified. The Turkish version of the MFES has excellent internal consistency (Cronbach's alpha, 0.978) and reliability (interclass correlation coefficient, 0.928–0.982), and its construct validity was supported by its ability to distinguish between the groups with respect to fall-risk factors and balance. According to the BBS scores, the high-fall-risk group had lower MFES scores than the moderate- and low-fall-risk groups (χ2 = 34.153, P = 0.001). The Turkish version of the MFES is a sensitive instrument for evaluation of fall-related confidence while carrying out indoor/outdoor activities. It also predicts falls, reduced physical activity, balance and mobility problems, and restricted social participation and daily living activities.


The Effects of Smoking on Ultrasonographic Thickness and Elastosonographic Strain Ratio Measurements of Distal Femoral Cartilage.
Although adverse effects of smoking on bone health are all well known, data on how smoking interacts with cartilage structure in otherwise healthy individuals remains conflicting. Here, we ascertain the effects of cigarette smoking on sonoelastographic properties of distal femoral cartilage in asymptomatic adults. Demographic characteristics and smoking habits (packets/year) of healthy volunteers were recorded. Medial, intercondylar, and lateral distal femoral cartilage thicknesses and strain ratios on the dominant extremity were measured with ultrasonography (US) and real time US elastography. A total of 88 subjects (71 M, 17 F; aged 18-56 years, N = 43 smokers and N = 45 nonsmokers) were evaluated. Mean amount of cigarette smoking was 10.3 ± 8.9 (1-45) packets/year. Medial, intercondylar and lateral cartilage were thicker in smokers than nonsmokers (p = 0.002, p = 0.017, and p = 0.004, respectively). Medial distal femoral cartilage strain ratio was lower in smokers (p = 0.003). The amount of smoking was positively correlated with cartilage thicknesses and negatively correlated with medial cartilage strain ratios (p < 0.05). Femoral cartilage is thicker in smokers but has less strain ratio representing harder cartilage on the medial side. Future studies are needed to understand how these structural changes in the knee cartilage should be interpreted with regard to the development of knee osteoarthritis in smokers.


Biliary tract cancer: molecular biology of precursor lesions.
Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of the precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterize the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment. This review delves into the molecular mechanisms that initiate and promote the development of precursor lesions of intra- and extrahepatic cholangiocarcinoma and of gallbladder carcinoma. It addresses the genomic, epigenomic and transcriptomic landscape of these precursors, and provides an overview of animal and organoid models used to study them. In conclusion, this review summarizes the known molecular features of precancerous lesions in biliary tract cancer and highlights our fragmentary knowledge of the molecular pathogenesis of tumor initiation.


Elucidating cannabinoid biology in zebrafish (Danio rerio).
The number of annual cannabinoid users exceeds 100,000,000 globally and an estimated 9% of these individuals will suffer from dependency. Although exogenous cannabinoids, like those contained in marijuana, are known to exert their effects by disrupting the endocannabinoid system, a dearth of knowledge exists about the potential toxicological consequences on public health. Conversely, the endocannabinoid system represents a promising therapeutic target for a plethora of disorders because it functions to endogenously regulate a vast repertoire of physiological functions. Accordingly, the rapidly expanding field of cannabinoid biology has sought to leverage model organisms in order to provide both toxicological and therapeutic insights about altered endocannabinoid signaling. The primary goal of this manuscript is to review the existing field of cannabinoid research in the genetically tractable zebrafish model-focusing on the cannabinoid receptor genes, cnr1 and cnr2, and the genes that produce enzymes for synthesis and degradation of the cognate ligands anandamide and 2-arachidonylglycerol. Consideration is also given to research that has studied the effects of exposure to exogenous phytocannabinoids and synthetic cannabinoids that are known to interact with cannabinoid receptors. These results are considered in the context of either endocannabinoid gene expression or endocannabinoid gene function, and are integrated with findings from rodent studies. This provides the framework for a discussion of how zebrafish may be leveraged in the future to provide novel toxicological and therapeutic insights in the field of cannabinoid biology, which has become increasingly significant given recent trends in cannabis legislation.


[Implants and orthodontics].
After a detailed historical review of implantology applied to orthodontics, and an analysis of experimental studies on orthodontic implants, the authors assess the interest of implant clinical uses as anchorage for orthodontic movement, prosthetic supports in agenetic cases or retention devices after orthodontic therapy. Different specifications and requirements are also given for a multidisciplinary approach of treatment plants.


Extramedullary plasmacytoma presenting as upper back pain.
Extramedullary plasmacytoma (EMP) is a rare soft tissue plasma cell tumour, usually presenting as a mass within the upper respiratory tract. It is most unusual for it to present in the posterior mediastinum as a primary solitary lesion. Discussed here is the case report of a patient who initially presented with musculoskeletal pain. Subsequent investigations, however, revealed the cause to be an EMP; diagnosis was made on finding aggregates of plasma cells on histological examination of the tissue specimen. The latter had been obtained by way of a computerised tomography scan guided biopsy of the tumour. Bone marrow aspiration studies showed no evidence of multiple myelomatosis. There was significant clinical improvement in response to radiotherapy. It is possible that this might represent one of the first documented reports of a primary solitary EMP in the posterior mediastinum.


Development of gluten-free craft beer: Impact of brewing process on quality attributes and consumer expectations for sensory properties.
To date, few studies investigated the differences between the two main gluten-free (GF) brewing techniques, such as the use of enzymes and the use of unconventional GF grains in brewing, by consumer perspective. In this study a GF beer brewed with sorghum and quinoa, as brewing adjuncts, was compared to the enzymatic-treated counterpart, in order to evaluate the effect of deglutinization treatment on physicochemical, volatile, and sensory characteristics of final beer. Moreover, the influence of brewing process and raw materials information on consumers' sensory perceptions, willingness to buy (WTB) and willingness to pay (WTP) was also investigated (n = 105 consumers), under blind (B), expected (E), and informed (I) conditions. The enzymatic-treated sample showed comparable physicochemical attributes with the untreated counterpart, except for a significant reduction in color and foam stability (p < 0.05). Non-significant difference between samples was found in the overall liking, WTB, and WTP mean scores in all three sensory test conditions (p > 0.05). The information about the deglutinization treatment had a negative impact on overall liking (p < 0.01), although WTP for both samples was significantly higher in the informed test than in blind condition (p < 0.05). Overall, Check-All-That-Apply test results confirmed that the deglutinization treatment does not affect the beer sensory profile, even if the information about brewing ingredients and technologies may slightly influence the consumers' sensory perception. Therefore, this result proves that it is possible to produce a marketable GF beer, simply by partially replacing 40% of barley malt with unconventional GF grains, without using enzymes for gluten reduction purpose.


Investigation of intraoperative brain deformation using a 1.5-T interventional MR system: preliminary results.
All image-guided neurosurgical systems that we are aware of assume that the head and its contents behave as a rigid body. It is important to measure intraoperative brain deformation (brain shift) to provide some indication of the application accuracy of image-guided surgical systems, and also to provide data to develop and validate nonrigid registration algorithms to correct for such deformation. We are collecting data from patients undergoing neurosurgery in a high-field (1.5 T) interventional magnetic resonance (MR) scanner. High-contrast and high-resolution gradient-echo MR image volumes are collected immediately prior to surgery, during surgery, and at the end of surgery, with the patient intubated and lying on the operating table in the operative position. In this paper we report initial results from six patients: one freehand biopsy, one stereotactic functional procedure, and four resections. We investigate intraoperative brain deformation by examining threshold boundary overlays and difference images and by measuring ventricular volume. We also present preliminary results obtained using a nonrigid registration algorithm to quantify deformation. We found that some cases had much greater deformation than others, and also that, regardless of the procedure, there was very little deformation of the midline, the tentorium, the hemisphere contralateral to the procedure, and ipsilateral structures except those that are within 1 cm of the lesion or are gravitationally above the surgical site.


International electives in neurology training: a survey of US and Canadian program directors.
To ascertain the current status of global health training and humanitarian relief opportunities in US and Canadian postgraduate neurology programs. There is a growing interest among North American trainees to pursue medical electives in low- and middle-income countries. Such training opportunities provide many educational and humanitarian benefits but also pose several challenges related to organization, human resources, funding, and trainee and patient safety. The current support and engagement of neurology postgraduate training programs for trainees to pursue international rotations is unknown. A survey was distributed to all program directors in the United States and Canada (December 2012-February 2013) through the American Academy of Neurology to assess the training opportunities, institutional partnerships, and support available for international neurology electives. Approximately half of responding programs (53%) allow residents to pursue global health-related electives, and 11% reported that at least 1 trainee participated in humanitarian relief during training (survey response rate 61%, 143/234 program directors). Canadian programs were more likely to allow residents to pursue international electives than US programs (10/11, 91% vs 65/129, 50%, p = 0.023). The number of trainees participating in international electives was low: 0%-9% of residents (55% of programs) and 10%-19% of residents (21% of programs). Lack of funding was the most commonly cited reason for residents not participating in global health electives. If funding was available, 93% of program directors stated there would be time for residents to participate. Most program directors (75%) were interested in further information on global health electives. In spite of high perceived interest, only half of US neurology training programs include international electives, mostly due to a reported lack of funding. By contrast, the majority of Canadian programs that responded allow international electives, likely due to clearer guidelines from the Royal College of Physicians and Surgeons of Canada compared to the Accreditation Council of Graduate Medical Education. However, the number of both Canadian and US neurology trainees venturing abroad remains a minority. Most program directors are interested in learning more information related to global health electives for neurology residents.


Alteration of blood glucose levels in the rat following exposure to hyperbaric oxygen.
Findings regarding blood glucose level (BGL) on exposure to hyperbaric oxygen (HBO) are contradictory. We investigated the influence of HBO on BGL, and of BGL on latency to central nervous system oxygen toxicity (CNS-OT). The study was conducted on five groups of rats: Group 1, exposure to oxygen at 2.5 atmospheres absolute (ATA), 90 min/day for 7 days; Group 2, exposure to oxygen once a week from 2 to 6 ATA in increments of 1 ATA/wk, for a period of time calculated as 60% of the latency to CNS-OT (no convulsions); Group 3, exposure to 6 ATA breathing a gas mixture with a pO2 of 0.21; Group 4, received 10 U/kg insulin to induce hypoglycemia before exposure to HBO; Group 5, received 33% glucose to induce hyperglycemia before exposure to HBO. Blood samples were drawn before and after exposures for measurement of BGL. No change was observed in BGL after exposure to oxygen at 2.5 ATA, 90 min/day for 7 days. BGL was significantly elevated after exposure to oxygen at 6 ATA until the appearance of convulsions, and following exposure to 4, 5, and 6 ATA without convulsions (P < 0.01). No change was observed in BGL after exposure to 6 ATA breathing a gas mixture with a pO2 of 0.21. Hypoglycemia shortened latency to CNS oxygen toxicity, whereas hyperglycemia had no effect. Our results demonstrate an influence of HBO exposure on elevation of BGL, starting at 4 ATA. This implies that BGL may serve as a marker for the generation of CNS-OT.


Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum.
Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.


Microsphere embolization of nerve capillaries and fiber degeneration.
Polystyrene microspheres, the size chosen to plug capillaries and precapillaries, were injected into the arterial supply of rat sciatic nerves. They produced widespread segmental occlusion of capillaries in lower limb nerves. The clinical and pathologic effect was dose-related. One million microspheres produced selective capillary occlusion but no nerve fiber degeneration; approximately 6 million microspheres also produced selective capillary occlusion and associated foot and leg weakness, sensory loss, and fiber degeneration, beginning in a central core of the distal sciatic nerve; 30 million microspheres caused both capillary and arterial occlusion and a greater neuropathologic deficit. From these observations it is inferred that 1) occlusion of isolated precapillaries and capillaries does not produce ischemic fiber degeneration; 2) occlusion of many microvessels results in central fascicular fiber degeneration, indicating that these cores are watershed regions of poor perfusion; and 3) stereotyped pathologic alterations of nerve fibers and Schwann cells are related to dose, anatomic site, and time elapsed since injection.


Serum concentrations of adiponectin in patients with hyperthyroidism before and after control of thyroid function.
Thyroid hormone affects adipocyte function, which in turn influences lipid and carbohydrate metabolism. Adiponectin is one of the adipocytokines that regulates lipid and carbohydrate metabolism. The aim of our study was to evaluate circulating levels of adiponectin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate medication. One hundred and twenty patients with hyperthyroidism were recruited at the time of diagnosis. Measurements of free T4 (FT4), thyroid-stimulating hormone (TSH), thyrotropin binding inhibitor immunoglobulin (TBII), adiponectin, fasting blood glucose, fasting serum insulin, lipid profile, and body mass index (BMI) were taken before and after 6 months of medical treatment, at which point all patients were in a euthyroid state. Any change in BMI was strongly correlated with changes in serum-adiponectin levels (r = -0.789, p<0.001). Any change in serum FT4 was also correlated with changes in BMI and serum adiponectin levels (r = -0.254, p = 0.05 and r = 0.501, p = 0.029 respectively). After controlling for BMI changes, we found correlation also between serum FT4 and adiponectin (r = 0.29, p = 0.005). Multivariate-regression analysis still revealed BMI to be a statistically strong predictor for serum-adiponectin level (p<0.001). However, that analysis also revealed thyroid function level as another predictor (p = 0.029). Although BMI is the best predictor of adiponectin, that thyroid hormone might influence circulating levels of adiponectin.


The effects of the flipped classroom in teaching evidence based nursing: A quasi-experimental study.
Evidence-based nursing (EBN) has been an important training mechanism for improving the quality of clinical care. At present, the pedagogy focuses on the application of e-learning and team-based learning to enhance learners' engagement and learning effectiveness. This study applied the flipped classroom approach to conduct evidence-based nursing (EBN) teaching. The aim of this study is to elevate the learning effectiveness of the flipped classroom group to the traditional teaching group in terms of knowledge and self-efficacy in practice. A pretest-posttest nonequivalent control group with a quasi-experimental quantitative design. The study recruited 151 nurses, of whom 75 were in the control group and 76 were in the experimental group. During the EBN course, the control group received training via traditional pedagogy while the experimental group engaged the flipped classroom approach. The learning effectiveness of EBN knowledge and self-efficacy in practice were evaluated across the three time points: pre-course, post-course, and one month after the course. In both group the scores of the EBN knowledge and self-efficacy in practice improved after training. The scores of the experimental group increased significantly than in the control group. However, the scores declined in both groups one month after the course. Even so, the experimental group's score of self-efficacy in practice was still higher than that of the control group. The implementation of the flipped classroom approach and team-based learning effectively enhanced the learners EBN knowledge accumulation and self-efficacy in practice. The research results can be used as an important reference for improving clinical nursing teaching quality.


Intraoperative Red Blood Cell Transfusion in Infant Heart Transplant Patients Is Not Associated with Worsened Outcomes.
Red blood cell (RBC) transfusion is common during infant cardiac surgery. A previous report of pediatric heart transplant recipients showed that increased RBC transfusion volume was independently associated with increased length of intensive care unit stay. It is unclear whether transfusion to infants as a subgroup carries similar risks. This study investigated relationships between intraoperative RBC transfusion during heart transplantation and postoperative length of stay (LOS), morbidity, and mortality in infants. Retrospective analysis of medical records from infants <1 year old undergoing primary heart transplantation at Loma Linda University Medical Center from 1985 to 2012 was conducted. Exclusion criteria included preoperative exchange transfusion or extracorporeal membrane oxygenation. Data sought included patient characteristics; intraoperative RBC transfusion volume and cardiopulmonary bypass details; and postoperative vasoactive support, ventilator support, morbidity, LOS, and 30-day mortality. The relationship of RBC transfusion volume (mL/kg) to these postoperative variables was assessed by univariate analysis. Multiple regression analysis of postoperative LOS included variables that were independent predictors of LOS or associated with ≥10% change in the β-estimate for RBC effect. Data from 307 infants showed that most (66.8%) had single-ventricle physiology. Median age at transplant was 50 days, weight 3.95 kg, and intraoperative transfusion volume 109 mL/kg. Transfusion volume was inversely related to age and weight. Median postoperative LOS was 18.2 days. Univariate linear regression analysis of transfused volume showed no relationship to log-transformed postoperative LOS (F(1,305) = 0.00; P = 0.960; R = 0.000; β-coefficient = 0.004; 95% confidence interval = -0.1542 to 0.1623). Transfused volume was not related to 30-day mortality (difference -0.162; -0.048 to 0.371 mL/kg; P = 0.112) or to postoperative ventilator support (R = 0.047), but was greater in patients who required reoperation (difference -0.246; -0.494 to -0.025; P = 0.004). Multiple regression analysis for all patients revealed age, preoperative ventilator support, prolonged postoperative ventilatory or vasoactive support, transplant year, and 30-day mortality, but not major adverse events, to be significant confounding variables. Adjusting for these variables, transfused volume was not associated with prolonged postoperative LOS. In contrast to a prior report, we found no correlation between intraoperative RBC transfusion and postoperative LOS when studying only infants. Infants have maturing organ systems, less physiologic reserve, and increased surgical blood loss (evaluated as mL/kg) during cardiac surgery than their larger, older counterparts, distinguishing them from the general pediatric population. These differences require additional studies to determine the outcome impact of transfusion strategies in the infant subgroup.


Colorectal polypoid lesions and expression of vascular endothelial growth factor in a consecutive series of endoscopic and surgical patients.
Colorectal cancer incidence in patients undergoing screening protocols is decreasing because of the higher rate of discovered preneoplastic colonic lesions; however, adenomatous polyps may not always be removable endoscopically and surgery may still be necessary. The aim of this study was to assess the vascular endothelial growth factor expression in the different steps of colorectal carcinogenesis to explore its potential role as a marker of malignancy in polypoid lesions. A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Real-time reverse transcription polymerase chain reaction for VEGF-A messenger RNA expression and immunohistochemistry for VEGF-A were performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Non-parametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. VEGF-A messenger RNA expression was higher in patients with high-grade dysplasia or colorectal cancer than in those with low-grade dysplasia adenomas (p = 0.01). At immunohistochemistry, VEGF-A expression was significantly higher in colorectal cancer patients compared to dysplastic adenomas (p < 0.001), and the accuracy of VEGF-A expression for prediction of malignancy was 91.7 (95% confidence interval = 78.7-97.9). VEGF-C protein expression was lower in colorectal cancer patients than in simple adenomas (p = 0.02). VEGF-A levels were directly correlated to polyp size (rho = 0.73, p = 0.0062). Multivariate analysis demonstrated that malignancy and polyp size were independent predictors of VEGF-A mucosal levels. This study demonstrated that the VEGF-A expression changes along the colorectal carcinogenesis pathway showing a neat step up at the passage from high-grade dysplasia to invasive cancer. This feature might potentially be useful to stratify colorectal polyps in different risks of progression classes. Moreover, the high level of VEGF-A expression predicted the presence of lymphovascular invasion with good accuracy.


ANATOMICAL VARIATIONS OF THE CELIAC TRUNK: A SYSTEMATIC REVIEW.
The celiac trunk (CT) is one of the abdominal portion branches of the aortic artery and, together with the superior mesenteric and inferior mesenteric arteries, participates in the abdominal viscera vascularization through a series of anastomoses. Absence of CT or variation in the number of terminal branches implies in varied abdominal arteries origins, which may have implication in surgical approaches. To analyze the anatomical variations of the celiac trunk and possible associated surgical clinical implications. It is a systematic review of articles indexed in the PubMed, Lilacs, SciELO, Springerlink, Scienc Direct and Latindex databases from August to September 2017. Original articles involving the anatomical variations of the celiac trunk in humans were included. The presence/absence of the celiac trunk, the number of terminal branches and the place of origin of its branches in variant cases of the normal anatomical pattern, were considered for this study. At the end of the research, 12 articles were selected, characterized by sample, anatomical structure evaluation method and main results. The normal anatomical pattern was the most prevalent in most studies (75.0%). CT was absent in 41.7% of the findings. The most prevalent anatomical variation was the presence of CT with bifurcation (66.7%). It was also observed the origin of the common and splenic hepatic arteries from the mesenteric arteries (25.0%). The presence of only one branch (16.7%) and quadrifurcation (8.33%) were other findings. CT variations are not uncommon findings, with different anatomic variants being reported. Thus, the importance of knowing the possible variations of this structure is emphasized, which may have implications for surgical interventions and imaging studies related to the abdominal region.


Arrival and diversification of mabuyine skinks (Squamata: Scincidae) in the Neotropics based on a fossil-calibrated timetree.
The evolution of South American Mabuyinae skinks holds significant biogeographic interest because its sister lineage is distributed across the African continent and adjacent islands. Moreover, at least one insular species, Trachylepis atlantica, has independently reached the New World through transoceanic dispersal. To clarify the evolutionary history of both Neotropical lineages, this study aimed to infer an updated timescale using the largest species and gene sampling dataset ever assembled for this group. By extending the analysis to the Scincidae family, we could employ fossil information to estimate mabuyinae divergence times and carried out a formal statistical biogeography analysis. To unveil macroevolutionary patterns, we also inferred diversification rates for this lineage and evaluated whether the colonization of South American continent significantly altered the mode of Mabuyinae evolution. A time-calibrated phylogeny was inferred under the Bayesian framework employing fossil information. This timetree was used to (i) evaluate the historical biogeography of mabuiyines using the statistical approach implemented in BioGeoBEARS; (ii) estimate macroevolutionary diversification rates of the South American Mabuyinae lineages and the patterns of evolution of selected traits, namely, the mode of reproduction, body mass and snout-vent length; (iii) test the hypothesis of differential macroevolutionary patterns in South American lineages in BAMM and GeoSSE; and (iv) re-evaluate the ancestral state of the mode of reproduction of mabuyines. Our results corroborated the hypothesis that the occupation of the South American continent by Mabuyinae consisted of two independent dispersion events that occurred between the Oligocene and the Miocene. We found significant differences in speciation rates between the New World and the remaining Mabuyinae clades only in GeoSSE. The influence of phenotypic traits on diversification rates was not supported by any method. Ancestral state reconstruction suggested that the ancestor of South American mabuyine was likely viviparous. Our analyses further corroborated the existence of a transoceanic connection between Africa and South America in the Eocene/Oligocene period (Atlantogea). Following colonization of the isolated South America and subsequent dispersal through the continent by the ancestral mabuyine stock, we detected no difference in macroevolutionary regimes of New World clades. This finding argued against the ecological opportunity model as an explanation for the diversity of living mabuyines.


Patient factors associated with hemoglobin A1C change with pioglitazone as adjunctive therapy in type 2 Diabetes Mellitus.
To identify patient factors associated with change in hemoglobin A1C (A1C) with adjunct pioglitazone therapy in routine clinical practice. This was a retrospective analysis of adult type 2 diabetes mellitus patients in a health maintenance organization setting who were newly-initiated on pioglitazone between January 2002 and December 2005. Eligible patients were receiving at least one other oral antihyperglycemic medication prior to initiating pioglitazone and maintained a stable dose of pioglitazone for 90 days. Data on eligible patients' characteristics, pharmacy purchases, comorbidities, and A1C measurement 90 days prior to the pioglitazone purchase date (baseline) and 90 days after achieving a stable dose (follow-up) were obtained from electronic records. Multivariate regression modeling was used to assess factors independently associated with: 1) absolute change in A1C, 2) achieving a ≥1 percentage point decrease in A1C, and 3) achieving an A1C<7%. Baseline and follow-up A1Cs were available for 128 patients. At baseline, mean age was 65 years, 38% were female, mean A1C was 8.4%, and 74% had an A1C>8%. At follow-up, the mean A1C change was -1.2 percentage points (interquartile range= -0.4, -2.1), 59% achieved a ≥1 unit decrease in A1C, and 44% achieved an A1C<7%. Independent predictors in all models were baseline A1C and time (in days) between baseline and follow-up A1C measurements (p<0.05). Adjunct pioglitazone therapy in routine clinical practice was associated with clinically meaningful reductions in A1C levels. Patients with higher baseline A1C achieved the greatest absolute reduction in A1C but were less likely to achieve levels <7%.


Adipose tissue-derived stem cells ameliorate diabetic bladder dysfunction in a type II diabetic rat model.
Diabetes mellitus is associated with a broad constellation of voiding complaints that are often multifactorial and resistant to currently available therapies. The leading causes of diabetic bladder dysfunction (DBD) include alterations in the bladder smooth muscle, neuronal degeneration, and urothelial dysfunction. Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stromal cells, have shown promise as a novel tissue regenerative technique that may have utility in DBD. The aim of this study is to determine the efficacy and mechanism by which ADSCs may ameliorate DBD in rats fed a high-fat diet and treated with low-dose streptozotocin to induce type II diabetes. Improved voiding function was noted in ADSCs-treated rats as compared with phosphate-buffered saline-treated rats. Though some ADSCs differentiated into smooth muscle cells, paracrine pathway seems to play a main role in this process, thus resulting in reduction of apoptosis and preservation of "suburothelial capillaries network."


DNA assembly and enzymatic cutting in solutions: a gold nanoparticle based SERS detection strategy.
The ability to monitor biomolecular recognition such as DNA hybridization and enzymatic reactivity in solutions with high sensitivity is important for developing effective bioassay strategies. Surface enhanced Raman scattering (SERS) based on use of solid substrates to produce the SERS effect for the detection often requires substrate preparation which is ineffective for rapid monitoring. This report describes a new strategy exploiting a gold nanoparticle (AuNP) based interparticle "hot-spot" for SERS monitoring of DNA mediated assembly and enzyme induced cleavage of the assembly in solution phase. The DNAs consist of two different complementary DNA strands with a thiol modification for attachment to AuNPs of selected sizes. In a solution containing AuNPs conjugated with one of the single-stranded (ss) DNA and other AuNPs labeled with a Raman reporter molecule, 4-mercaptobenzoic acid (MBA), the introduction of the complementary DNA strand leads to a linkage of the two types of AuNPs, producing double-stranded (ds) DNA-AuNP assembly (ds-DNA-AuNPs) with an interparticle "hot-spot" for SERS detection of the diagnostic bands of the reporter. Upon introducing a restriction enzyme (e.g. MspI) into the ds-DNA-AuNP assembly solution, the removal of the interparticle "hot-spot" due to restriction enzyme cleavage of the ds-DNA leads to a decrease of the SERS signals. While the detailed cleavage process may depend on the reaction time and the amount of enzyme, the viability of using gold nanoparticle "hot-spot" based SERS monitoring of DNA assembly and enzyme cleavage is clearly demonstrated, which has important implications for developing new strategies for bioassays.


Measurement of stroke volume from pulmonary artery pressure record in man.
Stroke volume was determined from the pulmonary artery pressure record by application of the pulse contour method. Pulmonary artery pressure records were obtained in 17 patients using a high fidelity catheter-tip pressure transducer and simultaneous measurements of cardiac output were obtained from indicator dilution curves. The formula used was SV = KP sa (i plus T s/Td) where Psa is the planimetered area beneath the systolic portion of the pulmonary artery pressure curve. Ts and Td are the durations of systole and diastole, and K is a constant. Stroke volume was altered by isometric handgrip exercise and/or pharmacological agents in 15 patients. Serial measurementswere made in 2 patients in acute pulmonary oedema after myocardial infarction. Comparison of a wide range of values of stroke volume by the pulse contour method with those obtained from dye dilution curves showed a good correlation (r plus 0.97, P smaller than 0.001) regression line y = 1.01 times - 0.47. Measurement of stroke volume from the pulmonary artery pressure contour is a technique of potential value in serial haemodynamic monitoring.


Sequence analysis of the hemagglutinin gene of H9N2 Korean avian influenza viruses and assessment of the pathogenic potential of isolate MS96.
Sequence analysis of the hemagglutinin (HA) gene of five Korean H9N2 avian influenza virus (AIV) isolates showed that these viruses were closely related and possibly came from the same source. Phylogenetic analysis of the HA1 subunit of H9 subtype isolates revealed that Korean AIV isolates were different from isolates from the poultry markets in Hong Kong in 1997. None of the Korean AIVs had multiple basic amino acids at the HA cleavage site that confer high pathogenicity to some H5 and H7 AIVs. Phylogenetic analysis of the nucleoprotein and matrix gene demonstrated that Korean isolates cluster with Eurasian origin AIVs. The pathogenic potential of one of the isolates (MS96) was assessed after several passages in 14-day-old embryonated chicken eggs (ECE). Fourteen-day-old ECE derivatives of MS96 showed increased HA titer and embryo mortality in eggs; this was apparent after the third passage in 14-day-old ECE. Sequence analysis of the cleavage site of MS96 after the third and tenth passages in 14-day-old ECE revealed no changes in the amino acid sequence. The pathogenicity of MS96 after the tenth passage in 14-day-old eggs (MS96p10(ECE14)) was tested with 4-wk-old specific-pathogen-free chickens. The 14-day-old derivative, MS96p10(ECE14), showed wider tissue tropism and induced more severe clinical signs than the parent virus. Furthermore, after intranasal inoculation of 86-wk-old broiler breeders and 30-wk-old layers, the MS96p10(ECE14) derivative induced more severe signs of depression than the parent virus as well as a transient drop in egg production.


The Relationship between Renal Function and Bone Marrow Density in Healthy Korean Women.
The relationship between renal function and bone mineral density (BMD) is controversial. We evaluated the relationship between markers of renal function and BMD in healthy Korean women. A total of 1,093 women who visited the health promotion center at Pusan National University hospital were included in the cross-sectional study. We divided the study population into two groups by BMD: osteopenia-osteoporosis and normal in the lumbar and femur regions, respectively. We compared the relationship between renal function and BMD using a logistic regression model and used SAS 9.3 (SAS Institute, Inc., Cary, NC, USA) for all statistical analysis. Blood urea nitrogen (BUN), creatinine, and cystatin C (Cys-C) were correlated with BMD in both the normal and osteopenia-osteoporosis groups, and in logistic regression analysis, BUN and Cys-C were correlated with lumbar and femur BMD. However, after we adjusted for age, menopause, and body mass index, only creatinine showed a negative correlation with lumbar BMD, and estimated glomerular filtration rate (eGFR) was related positively with femur BMD. Serum creatinine could be a marker for lumbar BMD and eGFR for femur BMD in Korean women without overt nephropathy.


Enclosure environment affects the activity budgets of captive Japanese macaques (Macaca fuscata).
Individuals adapt to changes in their environment, such as food availability and temperature, by adjusting the amount of time spent in different behavioral activities. These adjustments in behavior should vary across age-sex class according to specific physiological and social needs. We studied the activity budgets of three social Japanese macaque groups inhabiting either vegetated or nonvegetated enclosures in order to compare the effects of access with vegetation, as both food and substrate on resting, feeding, grooming and moving activities over a 12-month period. Daily access to natural foods for monkeys in the vegetated enclosure seems to be largely responsible for the differences in daily time budgets of these three groups. Resting time in all three groups was longer than the time devoted to other activities. Resting and moving time in the two nonvegetated enclosures was significantly longer than in the vegetated enclosure. In contrast, feeding and grooming time was significantly longer in the vegetated enclosure. Seasonal variation in time spent feeding, resting and grooming was significantly effected by enclosure type. In all three enclosures, immatures, particularly females, spent more time feeding and moving, whereas adults spent more time resting. Significant monthly variation in time spent by age-sex class was noted only for feeding and resting. Interestingly, in the vegetated enclosure, time spent feeding on natural vegetation was equal to the amount of time spent feeding on provisioned food. This suggests that factors other than energetic and nutritional needs may be important determinants of the activity budget of the species. These results have important implications for the enrichment of captive primates and our understanding of the maintenance of activity patterns by primates in the wild.


Osteoblastoma of the nasal cavity arising from the perpendicular plate of the ethmoid bone.
The presence of a benign osteoblastoma in the ethmoid sinus is rare and only a few cases have been reported. This is a case of a benign osteoblastoma arising from the perpendicular plate of the ethmoid bone with extension to the nasal cavity. The diagnosis and management of this unusual lesion, as well as the histopathology and the imaging characteristics are reviewed. We also review the previously reported cases of benign osteoblastomas of different origin, with nasal cavity involvement.


Gastrointestinal polyps in McCune Albright syndrome.
McCune Albright syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease. Two MAS patients with perioral freckling, resembling Peutz-Jeghers syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis. Three of 4 subjects had documented GNAS mutations in peripheral blood. Genetic testing for STK11 and PRKAR1A genes was performed to exclude presence of coexistent PJS and Carney complex. Genetic testing of biopsy material was also performed. Hamartomatous gastrointestinal polyps with histological features similar to those in PJS were observed in all 4 subjects, only in the stomach and/or upper duodenum. Activating GNAS mutations were found in the polyps or adjacent mucosa in 3 of 4 subjects. One patient each had mutation only in the blood or tissue, while 2 patients had both. No subject harboured any detectable PRKARIA or STK11 mutation as determined by direct DNA sequencing and copy number variation analysis. These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients.


Extracellular vesicle-mediated delivery of circDYM alleviates CUS-induced depressive-like behaviours.
Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood-brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG-circDYM-extracellular vesicles (RVG-circDYM-EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG-circDYM-EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG-circDYM-EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that systemic administration of RVG-circDYM-EVs efficiently delivered circDYM to the brain, and alleviated CUS-induced depressive-like behaviours, and we discovered that RVG-circDYM-EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA-box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle-mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.


In Vitro Pluripotent Stem Cell Differentiation to Hepatocyte Ceases Further Maturation at an Equivalent Stage of E15 in Mouse Embryonic Liver Development.
Hepatocyte-like cells (HLCs) can be derived from pluripotent stem cells (PSCs) by sequential treatment of chemical cues to mimic the microenvironment of embryonic liver development. However, these HLCs do not reach the full maturity level of primary hepatocytes. In this study, we carried out a meta-analysis of cross-species transcriptome data of in vitro differentiation of human PSCs to HLCs and in vivo mouse embryonic liver development to identify the developmental stage at which HLC maturation was blocked at. Systematic variations were found associated with the data source and removed by batch correction. Using principal component analysis, HLCs from different stages of differentiation were aligned with mouse embryonic liver development chronologically. A "unified developmental time" (DT) scale was developed after aligning in vitro HLC differentiation and in vivo embryonic liver development. HLCs were found to cease further maturation at an equivalent stage of mouse embryonic day (E)13-15. Genes with discordant time dynamics were identified by aligning in vivo and in vitro data set onto a common DT scale. These genes may be targets of genetic intervention for enhancing the maturity of PSC-derived HLCs.


Predicting coronary heart disease in siblings--a multivariate assessment: the Framingham Heart Study.
The incidence of clinically recognized coronary heart disease and its relation to risk factors have been studied for 596 sibships in the Framingham Heart Study cohort. Only the 186 pairs of brothers were considered in the multivariate analysis, since the rate of coronary heart disease in women is low. Multiple logistic regression was performed by using endpoints of coronary heart disease as the dependent variable for the younger brother of the pair. Age, Metropolitan relative weight, systolic blood pressure, total cholesterol, cigarette smoking and endpoints of coronary heart disease for the older brother represent the independent variables. The incidence of myocardial infarction in the older brother is significantly related to myocardial infarction experience of the younger brother, even after the strong effects of total cholesterol, systolic blood pressure and cigarette smoking were controlled. These findings suggest that family history of myocardial infarction may be an important independent predictor of myocardial infarction, and suggest that familial aggregation for coronary heart disease may result from predisposition to disease, possibly genetic, that is not reflected in the measured levels of total cholesterol, systolic blood pressure or cigarette smoking.


[Mechanism of the effect of sera from rats subjected to high external temperature on rosette formation by splenic lymphocytes from non-immune animals].
Serum of rats subjected to the action of moderately high external temperature increased the immunogenicity of heterologous erythrocytes, but became inactive at a temperature of 2 degrees C and after the treatment with a polyvalent proteinase inhibitor--trasilol. Incubation of sheep erythrocytes with the serum of heated rats intensified the reaction of rosette formation by the lymphocytes of the spleen of intact rats. Incubation of the spleen cells with the sera of intact and heated rats failed to influence the rosette formation. After trasilol treatment the serum of heated rats completely lost the property to intensify the reaction of rosette formation. Phenomenon of intensification of rosette formation was revealed in case of treatment of erythrocytes with the sera at a temperature of 37 degrees C and was not reproduced at a temperature of 2 degrees C. Investigations carried out indicated that the increase in the immunogenicity of sheep erythrocytes and the intensification of their binding with the lymphocyte receptors of intact rats under the effect of the serum of heated animals were caused by the action of the same factor.


Aberrant nuclear β-catenin distribution does not prognosticate recurrences of endometrioid endometrial cancers - A retrospective single-institutional study.
Aberrant β-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer. This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed. 297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant β-catenin distribution was found in 135 patients (45.5%) and wild type membranous β-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant β-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between β-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected. Aberrant β-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts.


The Potential of Endophytes in Improving Salt-Alkali Tolerance and Salinity Resistance in Plants.
Ensuring food security for the global population is a ceaseless and critical issue. However, high-salinity and high-alkalinity levels can harm agricultural yields throughout large areas, even in largely agricultural countries, such as China. Various physical and chemical treatments have been employed in different locations to mitigate high salinity and alkalinity but their effects have been minimal. Numerous researchers have recently focused on developing effective and environmentally friendly biological treatments. Endophytes, which are naturally occurring and abundant in plants, retain many of the same characteristics of plants owing to their simultaneous evolution. Therefore, extraction of endophytes from salt-tolerant plants for managing plant growth in saline-alkali soils has become an important research topic. This extraction indicates that the soil environment can be fundamentally improved, and the signaling pathways of plants can be altered to increase their defense capacity, and can even be inherited to ensure lasting efficacy. This study discusses the direct and indirect means by which plant endophytes mitigate the effects of plant salinity stress that have been observed in recent years.


Comparative Age-Based Prospective Multi-Institutional Observations of 12,367 Patients Enrolled to the American College of Surgeons Oncology Group (ACOSOG) Z901101 Trials (Alliance).
The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients. This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts. The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3-1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7-1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30-0.70; p < 0.0001). Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.


Nosema notabilis (Microsporidia), its ultrastructure and effect on the myxosporean host Ortholinea polymorpha.
Nosema notabilis Kudo, 1939 produces chain-forming meronts with a dense cell coat in direct contact with the host cell cytoplasm. Cytoplasmic microtubules and membranaceous whorls could be observed in meront cytoplasm. Sporonts differ in that they have a thicker cell wall and more conspicuous endoplasmic reticulum (ER) cisternae. Sporoblasts have an externally ridged cell wall. Spores have an apically located anchoring disc, an isofilar polar tube with 6 to 9 turns and polyribosomal strands in the sporoplasm. Diplokarya occur in all stages. Heavily infected plasmodia of Ortholinea polymorpha (Davis, 1917) reveal marked pathological signs. The most prominent are reduction of surface projections and/or pinocytosis, inflated mitochondria with altered inner structures, affected vegetative nuclei, damage to generative cells and occurrence of various anomalous formations in the plasmodium cytoplasm. The damage may result in complete disintegration of the plasmodium. However, the development of the microsporidian is affected by a remarkably high percentage of teratological stages revealing membranaceous and tubular structures.


Scene power spectra: the moment as an image quality merit factor.
Coherent optical power spectra of random scene imagery can become a powerful image evaluation technique when properly analyzed. A normalized low order moment of power spectra is set forth as a good image quality merit factor, which also has the advantageous property of taking out the spectrum analyzer's aperture effect. In addition to the relevant theory, experimental results with this merit factor of power spectra are given that demonstrate a high degree of correlation with subjective quality rankings, as well as the accurate assessment of optimum focus.


Sequence analysis of a 50 kb region between spo0H and rrnH on the Bacillus subtilis chromosome.
The 49630 bp spo0H-rrnH region of the Bacillus subtilis genome has been fully sequenced. The sequence contains one partial and 62 complete ORFs, one partial and three complete rRNA genes and a cluster of six tRNA genes. The direction of the transcription and translation of 61 ORFs is the same as that of the movement of the replication fork. A homology search of 40 ORFs in newly determined sequence revealed that 27 of them had significant similarity to known proteins such as elongation factor G, elongation factor Tu, pseudouridine synthase I and ribsosomal proteins. Two adjacent genes, ybaD and ybaE, appeared to encode proteins belonging to the ATP-binding cassette (ABC) family.


Perfusion patterns in postictal 99mTc-HMPAO SPECT after coregistration with MRI in patients with mesial temporal lobe epilepsy.
To assess patterns of postictal cerebral blood flow in the mesial temporal lobe by coregistration of postictal 99mTc-HMPAO SPECT with MRI in patients with confirmed mesial temporal lobe epilepsy. Ten postictal and interictal 99mTc-HMPAO SPECT scans were coregistered with MRI in 10 patients with confirmed mesial temporal lobe epilepsy. Volumetric tracings of the hippocampus and amygdala from the MRI were superimposed on the postictal and interictal SPECT. Asymmetries in hippocampal and amygdala SPECT signal were then calculated using the equation: % Asymmetry =100 x (right - left) / (right + left)/2. In the postictal studies, quantitative measurements of amygdala SPECT intensities were greatest on the side of seizure onset in all cases, with an average % asymmetry of 11.1, range 5.2-21.9. Hippocampal intensities were greatest on the side of seizure onset in six studies, with an average % asymmetry of 9.6, range 4.7-12.0. In four scans the hippocampal intensities were less on the side of seizure onset, with an average % asymmetry of 10.2, range 5.7-15.5. There was no localising quantitative pattern in interictal studies. Postictal SPECT shows distinctive perfusion patterns when coregistered with MRI, which assist in lateralisation of temporal lobe seizures. Hyperperfusion in the region of the amygdala is more consistently lateralising than hyperperfusion in the region of the hippocampus in postictal studies.


[Delusional parasitic infestation and folie à deux: case report].
Shared psychiatric disorder (folie deux) is a rare condition. But its prevalence can be 5-25% in patients with delusional parasitic infestation. We report the a case of a 62 years-old female with psychotic symptoms. For 15 years, she has lived with her younger sister. Since the patient was well-controled, her sister interrupted her antipsychotic drug administration. So, the patient initiated delusional parasitic infestation accompanied by visual hallucinations. Her sister, who did not have psychiatric history, initiated to believe that the patient was really infested. Moreover, she started to believe that was infested by the patient. This case report aims to discuss the relation between folie deux and delusional parasitic infestation.


Familial sarcoma: challenging pedigrees.
Partially due to the rare occurrence of soft tissue and osteogenic sarcomas in the general population, scant attention has been given to their hereditary etiology. Their overall poor prognosis might be ameliorated through an understanding of their environmental and hereditary causal factors, and/or their interactions, thereby contributing to earlier diagnosis and even the development of molecularly based targeted therapy. The authors selected 10 sarcoma-prone families from their extensive hereditary cancer-prone family resource and focused on their challenging diagnostic, surveillance, and management features. The family study protocol included the compilation of a detailed family history of malignant disease of all anatomic sites and the collection of all available primary medical and pathology documents for verification. Genetic counseling was provided before DNA collection and at disclosure of results. These families displayed marked phenotypic and genotypic heterogeneity. In one of these families, 16 relatives had sarcomas, with 2 of the 16 each having 2 metachronous sarcomas; to our knowledge, this represents the greatest number of sarcomas reported in any family described to date. Two familial atypical multiple-mole melanoma syndrome kindreds with the CDKN2A mutation showed the association of sarcoma with malignant melanoma, whereas one family had several pancreatic carcinomas. Other families with sarcoma had hereditary nonpolyposis colorectal carcinoma with MSH2 mutation, hereditary breast carcinoma with BRCA1 mutation, and p53 mutation in a Li-Fraumeni syndrome. Sarcoma-prone families reported in the current study were selected carefully to depict clinicopathology and compliance features, the understanding of which could elucidate the etiologic role of genetic factors in concert with the phenotypic and genotypic heterogeneity encountered in such families. The lack of a population-based data set for these families posed a limitation.


Immunohistological evaluation of alopecia areata treated with squaric acid dibutylester (SADBE).
A total of 19 patients with alopecia areata volunteered for serial biopsies of the scalp skin during SADBE treatment. Regrowth of terminal hair was seen in 12 of the 19 patients on the side of the scalp treated with SADBE for a minimum of four months, but not on a control side treated with sodium lauryl sulphate (SLS). Immunocompetent cells were characterized with ANAE staining and monoclonal antibodies in biopsy specimen showing marked peribulbar and perivascular inflammatory cell infiltrates. Inflammatory cell subclasses were repeatedly evaluated during SADBE treatment. No specific alterations in lymphocyte subclasses and macrophages were seen in relation to the hair growth response. In immunofluorescent studies it was found that in patients with regrowth of hair, immunoglobulins, fibrin and complement, appeared in the hair bulb and along the basement membrane during the treatment. Results were negative in patients without regrowth of terminal hair and in SLS-treated skin. As we could not demonstrate that any cell-mediated mechanism was involved, we suggest that SADBE may induce terminal hair growth through as yet uncharacterized mediators.


Oxfendazole pulse release intraruminal devices and bovine parasitic bronchitis: comparison of two control strategies in a field experiment.
Lungworm-infected seeder calves were used on two 1.41 ha paddocks to ensure that groups of 11 susceptible trial calves would be exposed to heavy early season challenge with Dictyocaulus viviparus. This produced conditions for an artificially severe test of two control strategies. The first employed a front-loaded oxfendazole pulse release bolus, ie, an intraruminal device which released one therapeutic anthelmintic dose immediately and five subsequent pulses at approximately three-weekly intervals. These front-loaded boluses were given to five of 11 calves on one paddock as soon as parasitic bronchitis had become clinically obvious (34 days after turnout) while the remaining six calves were kept as untreated controls. Clinical signs quickly subsided in the treated animals and no further respiratory problems occurred despite continued exposure to reinfection. The other control strategy involved the administration at turnout of an oxfendazole pulse release device which released the first of five anthelmintic doses approximately three weeks after administration, to all 11 calves on the other paddock. This strategy was almost completely successful in preventing patent infections from establishing and reduced the infectivity of the pasture in August and September by 94.1 per cent as shown by tracer calf studies. The calves treated at turnout performed better than the calves treated with the front-loaded boluses for most of the season and had an average weight-gain advantage of 20.4 kg at housing (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Analytical vectorial structure of hollow Gaussian beams in the far field.
The analytical vectorial structure of HGB is investigated in the far field based on the vector plane wave spectrum and the method of stationary phase. The energy flux distributions of HGB in the far-field, which is composed of TE term and TM term, are demonstrated. The physics pictures of HGB is illustrated from the vectorial structure, which is important to understand the theoretical aspects of both scalar and vector HGB propagation.


Exercising while pregnant.
Current literature on exercise and pregnancy was reviewed. Normal anatomic and physiological changes of pregnancy are briefly outlined. Benefits of maternal exercise experienced by the mother and fetus have been reported by some researchers. Other researchers have documented respiratory and cardiovascular changes peculiar to exercise during pregnancy. Effects on the fetus are also discussed. Guidelines for exercise during pregnancy are discussed with recommendations for health professionals caring for pregnant women. It is concluded that exercise during pregnancy can be safe if common sense is used and guidelines are followed. J Orthop Sports Phys Ther 1989;10(9):358-365.


Outlier or handover: outcomes for General Medicine inpatients.
Objective Patients admitted from the emergency department may be co-located on the treating team's 'home ward'. If no bed is available, patients may be sent to another ward, where they may remain under the admitting team as an 'outlier'. Conversely, care may be handed over to the team on whose home ward they are located. We conducted a retrospective analysis to understand the impact of outlier status and handovers of care on outcomes for General Medicine inpatients. Methods General Medicine admissions at the Royal Adelaide Hospital between September 2020 and November 2021 were analysed. We examined the rate of hospital-acquired complications, inpatient mortality rate, mortality within 48 h of admission, Relative Stay Index, time of discharge from hospital and rate of adverse events within 28 days of discharge. Results A total of 3109 admissions were analysed. Handovers within 24 h of admission were associated with a longer length of stay. There was a trend towards higher rates of adverse events within 28 days of discharge with handovers of care. Outlier status did not affect any outcome measures. Conclusions Handovers within the first 24 h of admission are associated with longer than expected length of stay.


Intraocular pressure and aqueous flow are decreased by cholera toxin.
Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2-fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood-aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP.


Outcome of twin birth. Review of 1,636 children born in twin birth.
During the five-year period 1964-68 96 733 births were registered in the 28 hospitals equipped with maternity facilities in the Uppsala hospital region. Of these babies, 1 636 were born in 818 twin deliveries. Data on gestational age, sex, weight and length at birth, birth order, hospital type, congenital malformations and perinatal mortality are analysed. Altogether 17.3 per 1 000 of the children born during this period were born in multiple births. The perinatal mortality for the twin babies was 64 per 1 000 born, with the mortality higher in the less specialized hospitals than the others. Twin no. 1 suffered perinatal death in 67 cases per 1 000 and twin no. 2 in 60 cases per 1 000. For twins of primiparae the losses were 92 per 1 000 children and for twins born to multiparae 51 per 1 000. Altogether 72 per 1 000 male twins died perinatally compared to 52 per 1 000 female twins. The most heavy losses occurred among the low-weight premature twins and in these cases both twins often suffered perinatal death.


Characterization of surface-modified nanoparticles for in vivo biointeraction. A sedimentation field flow fractionation study.
Sedimentation field flow fractionation (SdFFF) is an emerging high-performance analytical tool for separation and determination of size and adsorption characteristics of colloidal particles. This study demonstrates how SdFFF can be used to characterize nanoparticles prepared for in vivo applications including (1) the quantification of polymer uptake on nanoparticles where surface coverage is crucial and (2) the coupling of cell adhesive peptides containing the Arg-Gly-Asp motif (RGD). Quantitative information about polymer adhesion in order to prepare a bioinert surface and an accurate determination of ligand uptake are both of obvious importance for the understanding of, for example, relations between the number of attached molecules for biointeraction and an observed therapeutic effect. In addition, the present work highlights the necessity to perform careful characterization of commercially available particulate starting materials, in terms of size and polydispersity, prior to biological experimentation.


Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii.
Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 μg/ml). Time-kill studies were performed over 24 h using approximately 10(6) CFU/ml of each strain with clinically relevant minocycline concentrations (2 μg/ml and 8 μg/ml), with and without polymyxin B (0.5 μg/ml). The in vivo efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥ 4×) was observed in the presence of PAβN. The intracellular concentration and in vitro bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.


Proteomics Profiling of Pancreatic Cancer and Pancreatitis for Biomarkers Discovery.
Pancreatic cancer is one of the most aggressive malignancies with an increase in incidence predicted, particularly in African Americans. Pancreatic cancer is considered a silent disease with poor prognosis and a lack of early biomarkers for detection. Proteomics has been applied in many diseases for identifying or discovering biomarkers. It has long been suggested that chronic pancreatitis may be a risk factor for developing pancreatic cancer. This study identified proteins that are altered in expression in pancreatic cancer and pancreatitis compared to normal using proteomic technology. Proteins were extracted from laser captured micro-dissected tissues and separated in 2-DPAGE and imaged. The protein profiles of pancreatic cancer and pancreatitis are similar but differed with the protein profile of normal adjacent tissues. Representative proteins, overexpressed in tumor and pancreatitis but not normal tissues, were excised from gels, subjected to in-gel digestion, and analyzed by MALDI-TOF mass spectrometry. Proteins identified included transferrin, ER-60 protein, proapolipoprotein, tropomyosin 1, alpha 1 actin precursor, ACTB protein, and gamma 2 propeptide, aldehyde dehydrogenase 1A1, pancreatic lipase and annexin A1. Several proteins, which were shown in pancreatic cancer, were also observed in pancreatitis samples. Understanding the role of these specific proteins and their mechanistic action will give insights into their involvement in pancreatic cancers.